How Will Payers and Physicians Respond to Novel Agents
in Late-Stage Clinical Development for Pulmonary Hypertension?

Introduction:

Pulmonary hypertension (PH) constitutes a group of rare
diseases, yet the commercial potential for novel drugs approved for it is
considerable, driven by the premium prices that may be charged for drugs in
these indications. The late-stage pipeline for PH includes Bayer’s
first-in-class soluble guanylate cyclase (SGc) stimulator riociguat, Actelion’s
selexipag (oral non-prostanoid prostacyclin analogue), and Actelion’s Opsumit
(macitentan; novel endothelin receptor antagonist [ERA]).

At the annual CHEST meeting in October 2012, Actelion and
Bayer presented pivotal clinical trial results for their respective
investigational oral PH therapies, Opsumit and riociguat. Both therapies met
their Phase III primary end points, with Opsumit reducing the risk of a
mortality and/or morbidity event in pulmonary arterial hypertension (PAH)
patients compared with placebo, and riociguat demonstrating improvement in
exercise capacity in two separate trials conducted in PAH patients and in
patients with chronic thromboembolic pulmonary hypertension (CTEPH).

The lack of head-to-head trial data for current PH therapies,
either against one another or against agents in development, and a lack of data
in patient populations other than PAH, create an increasingly complex treatment
landscape. Pulmonologists face the challenge of considering each new therapy’s
unique balance of benefits, drawbacks, risks, and rewards when making treatment
decisions. Furthermore, the evolving reimbursement landscape and loss of market
exclusivity for the first oral PH therapies in the United States (sildenafil
[Pfizer’s Revatio] in 2012 and bosentan [Actelion’s Tracleer] in 2015), coupled
with the burgeoning number of available treatment options, will result in
increased market access challenges for PH therapies.

The entrance of these therapies will lead to the development
of a more complex marketplace for severe, refractory disease, leading
physicians and payers alike to make key decisions about which treatments to
prescribe or reimburse over others. This report examines the dynamics that will
limit or promote market access for new market entrants, employing the results from
our survey of 100 pulmonologists and 30 managed care organization (MCO)
pharmacy or medical directors.

Questions Answered in This Report:

*
Understand pulmonologists’ use of currently available PH
therapies. How do pulmonologists and payers differentiate between the
different oral, inhalable, and infused PH therapies? What are the key considerations
for physicians when selecting PH agents, and how does treatment differ for
different subpopulations of PH patients (e.g., PAH, CTEPH, or PH due to left
ventricular dysfunction [LVD])? What restrictions (e.g., step therapy) do
payers place on the use of current PH agents?

*
Explore pulmonologists’ and payers’ attitudes towards treating
PH as new therapies become available. How do surveyed pulmonologists expect
to incorporate Opsumit, riociguat, and selexipag into clinical practice? Where
do they expect these agents to sit in the changing treatment algorithm, and
which current PH therapies are most at risk of losing share? What factors will
most influence formulary inclusion of these emerging agents? How will MCO
reimbursement constraints, including tiering and formulary restrictions, impact
the potential patient share of these emerging drugs? Are data demonstrating a
benefit to morbidity/mortality an advantage in the eyes of payers for Opsumit,
and, conversely, is the absence of such data a hindrance for riociguat?

*
Examine pulmonologists’ and MCO PDs’ receptivity to and
expectations for generic versions of older PH drugs such as sildenafil and
epoprostenol. How do pulmonologists expect to incorporate such agents into
clinical practice should they reach the market? How will this impact the
branded agents? What, if any, will be the impact on other branded PH drugs? How
do MCO PDs expect to position generic sildenafil and generic epoprostenol on
their formularies, what restrictions will they impose, and how will branded
agents be affected?

Scope:

This U.S. Physician & Payer Forum investigates payer and
physician dynamics that affect prescribing practices for therapies for PH in
the United States. The report is based on a survey of 100 pulmonologists and 30
pharmacy/medical directors at MCOs that offer commercial health insurance. We
analyze current physician and payer insights and practices; perceptions of
biologics and Spiriva in the pipeline; uptake of emerging therapies for severe,
refractory asthmatics; and formulary decision making for current and emerging
agents, including Actelion’s Tracleer, Gilead’s Letairis, Pfizer’s Revatio,
United Therapeutics’ Adcirca, GlaxoSmithKline’s Flolan, Actelion’s Veletri,
United Therapeutics’ Remodulin, Actelion’s Ventavis, and United Therapeutics’
Tyvaso.